title: The role of MAPK pathway in bone and soft tissue tumors.
abstract: OBJECTIVE
  Expression of mitogen-activated protein kinase (MAPK) signaling and its role in cell proliferation of the bone malignancies, osteosarcoma (OS) and malignant fibrous histiocytoma (MFH) were investigated.
  
  
  METHODS
  Gene expression and protein levels of RAF1 and MEK1/2 in 6 human sarcoma cell lines and 7 surgically obtained OS specimens were assessed by RT-PCR and immunohistochemistry, respectively. MEK inhibitor, U0126 [1,4-diamino-2,3-dicyano-1,4-bis (2-aminophynyltio) butadiene], was used for cell proliferation assays.
  
  
  RESULTS
  RAF1 and MEK 1/2 mRNA was detected in all cell lines and OS specimens. RAF1, MEK 1/2 and p-MEK protein was also expressed in the cells, as was MEK1/2 in OS specimens. Treatment with U0126 resulted in dose- and time-dependent inhibition of cell proliferation and suppression of p-ERK expression, opposite to promotion of p-MEK.
  
  
  CONCLUSIONS
  U0126 blocks MAPK signaling and decreases cell proliferation in OS and MFH. Thus, selective MAPK inhibitors might be therapeutically advantageous in the treatment of bone and soft tissue sarcomas.
authors.affiliation: Department of Orthopaedic Surgery, Kagawa University, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. sasakan1@yahoo.co.jp
authors.forename: Kanji
authors.initials: K
authors.lastname: Sasaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hitora
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakamura
authors.forename: Ryouta
authors.initials: R
authors.lastname: Kono
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002070:Butadienes / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D051677:Histiocytoma, Malignant Fibrous / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D012516:Osteosarcoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D002070:Butadienes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C113580:U 0126; C482128:MAP2K2 protein, human; D019908:Proto-Oncogene Proteins c-raf; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human